The present study is designed to provide further understanding of and insight into the pathogenesis, mode of transmission, and factors associated with activation and/or persistence of cytomegalovirus infection using guinea pigs as an animal model. This model is unique for study of species specific virus in its homologous host in that the guinea pig possesses certain physical attributes that render them comparable to the human cytomegalovirus infection. Since the transplacental transmission of GPCMV in guinea pigs has been demonstrated, further studies will center on intrauterine infection, with special emphasis on obtaining evidence of neurologic sequelae in newborns. Parallel studies on virology and histopathology will be undertaken in order to obtain information regarding congenital infection. Host response to CMV infection in guinea pigs has not been previously explored; the proposal includes experiments for the determination of both viral persistence and effect of virus infection on cell mediated immune mechanisms. Finally, studies wll be carried out in an effort to assess the potential that an attenuated or subunit GPCMV vaccine has for protecting guinea pigs, especially the fetuses, from the consequences of GPCMV infection by conferring active immunity as the result of vaccination. The data obtained in these studies should be particularly useful in their application to the problems associated with human CMV infection and pathogenesis.